Experimental atrophic rhinitis (AR), serum antibody titres and in vitro lymphoproliferation to Pasteurella multocida derived toxin (Pm-T) were studied in piglets. Specific immune responses to Pm-T and Pm-T induced conchae atrophy were compared with AR immunity. This immunity was initiated by the Nobi-VAC AR-T vaccine administered at various times with respect to Pm-T challenge. Animals challenged with Pm-T developed conchae atrophy, but no antibodies nor cellular immune responses to Pm-T were detected. Vaccination 3 weeks before Pm-T challenge protected pigs against breakdown of nasal bony tissues. This protection was accompanied by an increase of serum antibodies and in vitro lymphoproliferation to Pm-T. Animals vaccinated 10 days before or after Pm-T challenge also had antibodies and cellular immune responses. However, these animals developed AR. In vitro, Pm-T appeared mitogenic for quiescent (non-immune) peripheral lymphocytes and Concanavalin A stimulated lymphocytes from some pigs. These in vitro lymphoproliferative responses could be partly abrogated by the addition of monomorphic anti-swine major histocompatibility complex class II DQ and DR specific monoclonal antibodies. We conclude that Pm-T is poorly immunogenic in vivo and does not initiate a protective Pm-T specific immune response. Pigs were protected from AR by vaccination, but protection was dependent on the timing of vaccine administration. We speculate that Pm-T modifies the immune response such that the response is not directed towards the toxin but to an unidentified component in the nose of piglets.